Antiviral drug "polyrem"
(57) Abstract:Usage: in medicine as a drug for the treatment of viral infections such as influenza and other acute respiratory infections, herpes, encephalitis. The essence of the invention: antiviral drug contains, wt%: as the active substance - salt-methyl-a(1-substituted)methylamine, and copolymer of vinyl alcohol and N-vinylimidazole acid 2,5 - of 92.7, and targeted supplements to 7.3 - 97,5. New drug Polyrem has prolonged antiviral effect, exhibits antioxidant properties, is an interferon inducer, has immunostimulatory effects. table 4. The invention relates to medicine and can be used as a drug for the treatment of viral infections such as influenza and other acute respiratory infections, herpes, encephalitis.Influenza and other acute respiratory infections remain the most common infections because of the unique variability of excitatory their viruses, and global epidemics of influenza.According to the who disease caused by the herpes simplex virus (HSV), second place (15,8%) after influenza (35,8%) as a cause of mortality from viral infections.Herpes is esni, the ability of herpes viruses to affect practically all organs and systems of the body, a variety of clinical forms with the development of latent, acute and chronic infections. Negative role have the herpes viruses in cancer development, induction of atherosclerosis, adverse impact on pregnancy and childbirth, leading to a high probability to chronic disease in children. The herpes viruses are a cofactor in the activation of HIV infection.Treatment of patients with chronic recurrent infection is difficult due to the ambiguity of the mechanisms of the disease, the diversity of clinical forms and frequent relapses, and also due to the lack of highly effective antiherpetic drugs (Principles of treatment of patients with simple herpes. Information and methodological letter. St. Petersburg: 1993; Isakov Century A. Ermolenko D. K. Black, M. D. Therapy hermetic infection. St. Petersburg: Hippocrates, 1993).The virus of tick-borne encephalitis occurs in natural conditions. Natural foci of tick-borne encephalitis disseminated widely. Risk of infection is exposed to about 20 million people. In some cases, the disease proceeds without complications, but there is often heavy is troist. At 1-3% after acute form of the disease remains a chronic pathology.The prevalence and severity of the disease dictate the need to create specific drugs for the prevention and treatment of tick-borne encephalitis.Prevention and treatment of such infectious diseases by immunization with inactivated or live vaccines do not provide reliable protection, the effectiveness of which is reduced due to the rapid variability of viral strains.It is therefore very important socio-economic importance is the development of highly effective drugs against viral respiratory infections, influenza, herpes infections, tick-borne encephalitis.Some progress is achieved when used for the prevention and treatment of viral infections derivatives of adamantane.Known antiviral drug containing as an active substance 1-adamantylamine hydrochloride amantadine (Ershov, F. I. Figov E. P., Tselakova E. B. Antiviral agents. SPb, 1993, S. 19; Amer. J. Med. - 1987. Y. 82, 6A, P. 35-41). Amantadine has a preventive effect against infections caused by virus type a, and leads to a decrease in clinical disease only when ranti and side effects, when developed infection treatment has no action.Currently in medical practice for the prevention and treatment of influenza antiviral agent rimantadine, containing as active substance hydrochloride-methyl-a(1-substituted)-methylamine. This drug is one of the most effective means of combating influenza infection (M. D. Mashkovsky. Medicinal product. M. Medicine, 1986, so 2, C. 380. Ershov, F. I. Chizhov N. P. Tselakova E. B. Antiviral agents. SPb, 1993, S. 35). However, the rapid elimination of the drug from the body requires frequent reception to maintain the required therapeutic dose. Increase a single dose leads to undesirable side manifestations and a little more efficient. Efficient use of rimantadine for prophylaxis of influenza during outbreaks also depends on the regularity of drug intake, which creates certain difficulties when conducting large-scale preventive measures (Pershin, N. Bogdanova N. With. Chemotherapy of viral infections. M. Medicine, 1973, S. 73).To overcome these difficulties may contribute to the use for the prevention and treatment of influenza and other vishnoi activity rimantadine against herpes virus are absent. Known antiviral agents adapromin, katiforis, Arbidol (Ershov, F. I. Chizhov N. P. Tselakova E. B. Antiviral agents. SPb, 1993, S. 15, 22, 29. Chizhov N. P. Anikin Century B. He, M.,// "The Doctor", 1993, N 3).Adapromin-(a-ethyl-a(1-substituted)methylamine) active against influenza viruses type a and b, but the toxicity of rimantadine.Cateforis (derived bicycloheptane) on the effectiveness of action comparable with rimantadine, but less toxic.These drugs do not exceed the validity period of rimantadine.Arbidol-(1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethyl-aminomethyl-5-hydroxy-6-bromoindole hydrochloride monohydrate), despite the recommendation of its use in herpes infection, the level of protection for influenza and other acute respiratory infections yielded rimantadine, depramine, deitiforina. Arbidol is more toxic and has a lower bioavailability compared with these drugs.In the treatment of herpesvirus infections known antiviral drug containing as an active substance 2-C-b-D-glyukopiranozil-1,3,6,7-tetracycine isolated from the underground parts of the Alpine Hedysarum or yellowing alpizarin. Alpizarin - toxic substance than the(from 200 to 40 depending on the severity of an infectious disease) compared with bonafton, cerecero, chemotherapeutic index are respectively equal to 2.5; 1.Alpizarin taking into tablets 0.1 g 3-4 times a day for 5-10 days and at the same time locally, by application apply 5% ointment on the skin or 2% ointment to the mucous membrane within 10-30 days (A. C. the USSR 1336301, 1988).Known antiviral drug with Antiherpes virus effect of the action, containing as active substance 5-iodine-2-dazoxiben (idoxuridine, GO). Idoxuridine applied in the form of a 0.1% aqueous solution for the treatment of keratitis caused by herpes simplex virus type 1 (Ershov, F. I. Chizhov N. P. Tselakova E. B. Antiviral agents. SPb, 1993, S. 30).Use the GO gives you a quick effect in the surface forms of lesion of cornea, limits the spread of infection, reduces inflammation, promotes healing of the affected cornea. After the local destination GO for the treatment of cutaneous herpetic diseases sometimes observed therapeutic effect, but in most cases the drug is ineffective.When systemic use ARE marked its toxicity, mutagenic effects and immunosuppressive effect. CR is selected to it of viruses.Anti-herpes action has antiviral drug containing as an active substance 9--arabinofuranosyl adenine (ARA-a or vidarabine). Vidarabine used for intravenous and intramuscular injection (Ershov, F. I. Chizhov N. P. Tselakova E. B. Antiviral agents. SPb. 1993, S. 26).Vidarabine compared with idoxuridine less toxic for systemic administration. However, the clinical application is limited due to the immunosuppressive actions and other side effects during system use.The most effective antiviral drug that has anti-herpes action, is a preparation containing as an active substance 9-(2-hydroxyl-ethoxymethyl)-guanine (acyclovir). Acyclovir is used in the form of tablets, powders and ointments.Acyclovir has advantages over other drugs due to their low toxicity and high selectivity of action on virousspecificakih syntheses, as under the action of acyclovir mainly disturbed virusinduced DNA synthesis in infected cells, and almost no changes DNA synthesis, the growing of intact cells. Especially valuable is that acyclovir is used in the about for successful prevention of recurrent herpes requires constant daily intake of the drug. Another significant drawback of acyclovir, as most Antiherpes virus effect of drugs, is relatively rapid formation to it resistant strains of herpes virus (Ershov, F. I. Chizhov N. P. Tselakova E. B. Antiviral agents. SPb, 1993, S. 23. M. R. Keating. Antiviral. Alents. // Mayo. lin. Proc. 1992. 67, No. 2. p. 160-178).Therefore a very important task is the development of highly complex products with long-term antiviral and immunostimulating action for the prevention and treatment of influenza, herpes and other viral infections.To solve videostalone technical challenges offered antiviral drug Polyrem, containing as active substance salt of a-methyl-a(1-substituted)-methylamine and copolymer of vinyl alcohol and N-vinylimidazole acid and the target additive in the following ratio, wt.The specified polymeric salt of a-methyl-a(1-substituted)methylamine 2,5oC 92,7
Additives target of 7.3oC 97,5
The active substance is produced by interaction of a-methyl-a(1-substituted)-methylamine with a copolymer of vinyl alcohol and N-vinylimidazole acid at ordinary temperature in an aqueous solution and equimolecular ratio in acetone or freeze drying of the solution.The copolymer of vinyl alcohol and N-vinylimidazole acid (SU-VAC) is a commercially available product and is produced under THE 40-2-170-88.a-Methyl-a(1-substituted)-methylamine is not a commercial product, an intermediate product in the synthesis of rimantadine hydrochloride. For the synthesis of Polyrem a-methyl-a(1-substituted)-methylamine (i.e., rimantadine-basis) was obtained from rimantadine hydrochloride (FS 42-1667-91) by treatment with a 5% aqueous solution of sodium hydroxide followed by extraction of rimantadine-base diethyl ether and distilled in vacuo (tKip100oC at 2 mm RT.cent.). Amantadinebuy is a colorless oily liquid, insoluble in water.The completeness of the reaction of the salt formation, the absence of free carboxilic groups (-COOH) is confirmed by the data of IR-spectra Polarama, in which there is no absorption band at 1720 cm-1corresponding to the deionized-COOH groups of the acid, and there are absorption bands at 1580-1610 cm-1responsible stretching vibrations of C-O in the ionized group-COO-. The resulting product has a molecular mass of 250005000 and contains 20-30% mol relatedentities units, which corresponds to di is The resulting substance is a white amorphous powder, odorless, bitter taste, soluble in water, in dilute hydrochloric and acetic acids, dimethylsulfoxide, practically insoluble in dimethylformamide, in 95% ethyl alcohol.< / BR>M. M. 25000 5000
n 25 5
m 100 n
Target additives necessary to obtain the antiviral drug in the form of a solid or ointment dosage forms. For solid dosage forms used pharmaceutically acceptable additives target, for example calcium stearate, microcrystalline cellulose, magnesium carbonate basic.Technology of production of solid dosage form consists in mixing the active substance with solid targeted supplements and subsequent pelletizing. Get tablets white color, bitter taste.Tablet polyrem weight of 0.15 g in the composition of the polymer substance at a constant dose of rimantadine-base 0.05 g contains 0,0685-0,0890 g of a copolymer of vinyl alcohol and N-vinylimidazole acid at a concentration of respectively 30oC 20% mol parts of N-vinylimidazole acid.Example 1. Composition per tablet, and Mac. (g):
Microcrystalline cellulose 6,3 (0,0095)
Example 2.Polyrem 79,0 (0,1185)
Remantadine-based 33,3 (0,05)
Copolymer of vinyl alcohol and N-vinylimidazole acid content of 30 mole% links acids of 45.7 (0,0685)
Magnesium carbonate basic 20,0 (0,0300)
Calcium stearate and 1.0 (0,0015)
Example 3.Polyrem 84,5 (0,1268)
Rimantadine-based 33,3 (0,05)
Copolymer of vinyl alcohol and N-vinylimidazole acid content of 25 mole% of units of acid 51,2 (0,0768)
Calcium stearate and 1.0 (0,0015)
Magnesium carbonate basic 14,5 (0,0217)
To obtain the antiviral drug in the form of ointments as the target additives used water-soluble or hydrophilic gelling ointment base, emulsifier, preservative, solvent.For emulsion or hydrogel bases use glycerin, sodium carboxymethylcellulose, methylcellulose, sodium alginate. As the emulsifier used a mixture of sodium salts of sulfate esters of high molecular weight alcohols with carbon atoms 16-18 with pure alcohols of the same faction in the ratio 3:7. Preservatives are nipagin ester Eloth. As the solvent used water.Technology of preparation of ointments is consistent mixing an aqueous solution of polyrem and preservative with emulsified or gel base.Used for treatment ointment containing 10; 5; 2.5% polyrem.Example 4. The ointment composition, wt.Polyrem 10
Methyl cellulose 2,5
Nipagin 0.1 to
Get 10% ointment polyrem.Example 5.Polyrem 5
Sodium carboxymethylcellulose 10
Get 5% ointment polyrem.Example 6.Polyrem 5
The methylcellulose 4
Example 7.Polyrem 2,5
The methylcellulose 4
Example 8.Polyrem 10
Sodium alginate 7
Example 9.Polyrem 10
Sorbic acid 0,2
Antiviral drug Polyrem for the prevention of influenza during the epidemic period and recurrent herpes is recommended to take 2 tablets (0.3 g) 1 every 3 days.In the treatment of herpes, during the acute period of 2 t is e drug locally only.In the treatment of flu on the first day of the disease is recommended once 4 tablets (0.6 g) in the second and third day 3 tablets.Laboratory tests on animals offered antiviral drug showed that the level of protective antiviral actions above the level of the corresponding action of rimantadine hydrochloride, and the index of protection is respectively 75 and 46% even after a single dose 24 h before infection.A pronounced protective effect of the drug polyrem seen within 48-72 h with index protection respectively 95-69%
Virusinghviru the drug entered once for 24, 48 and 72 h before infection animal virus A/Hong Kong/1/68, was much higher than the effect of rimantadine. If after administration of rimantadine was a decrease in the concentration of virus in the lungs compared with control 1.0-1.5 lg EID50then with the introduction of the proposed drug this value was 2.5-5.5 lg EID50(embryo infective dose).For clinical trials of polyrem was obtained permission from the Pharmacological Committee of Ministry of health USSR, Protocol N 3 from 14.02.90. Recommended to carry out tests on the basis of the research Institute of influenza Ministry of health, USSR, INSV strictly controlled observations in the clinical hospital with the introduction of volunteers vaccine strains with residual reactogenicity was established preferential and more pronounced protective effect of the proposed drug compared with rimantadine (PL.1). Once taking the drugs for 48 h prior to vaccination in individuals who offer drug polyrem, almost completely absent clinical response, whereas a single dose of rimantadine did not lead to a reduction in the overall number of reactions, nor the severity of their symptoms compared with the control group violence.In the case of receiving the drug for 72 h prior to vaccination total number of clinical reactions were halved, the protective effect of the drug was shown to 96 hoursThe drug has interferonogenna action. Interferonogenna activity polyrem with an average of 42 IU manifested in the period of taking the drug and up to 3 weeks after his admission.During the course of reception of a preparation for unbiased survey (blood pressure, pulse rate, biochemical composition of peripheral blood, electrocardiography data, the bioelectrical activity of the brain) physiological parameters remained within the normal range and did not change in comparison with the baseline data, which indicates a good tolerability of the drug and its safety.The results obtained in the study of the proposed drug in USLOVIYa surrounding preventive took 1 tablet of polyrem (50 mg in terms of rimantadine-base), 2 times with an interval of 72 h at rimantadine hydrochloride 50 mg daily for 5 days. In larger groups during epidemics to prevent polyrem took 2 tablets 1 every 3 days for 18 days. The effectiveness of the prevention of influenza epidemics as a result of taking polyrem more than 2 times higher than the efficiency in the use of rimantadine hydrochloride (PL.2). The index of effectiveness of the proposed drug with a high degree of confidence (p <0.01) in 2.1 times higher than the index of rimantadine hydrochloride.The results of clinical trials in the application of polyrem for treatment of influenza showed that
oral administration of polyrem influenza patients not cause side effects;
patients with laboratory-confirmed diagnosis of influenza type a polyrem has a therapeutic effect, manifested in the reduction of clinical symptoms and complications are more than 3 times; in patients with influenza type b, who polyrem in the same doses, cases complicated course of the disease is not detected;
polyrem normalizes immunological indicators of cellular immunity (T-helpers and T-suppressors and their ratio), increases the phagocytic and metabolic activity of cells, helping to reduce the number of complications.
olerem increases nonspecific resistance to viral and bacterial infections, that extends the range of application of the drug.Polyrem can be recommended as a means of prevention and treatment of influenza type a, type b and other mixed respiratory infections.The antiviral activity of the proposed tool against viruses of the herpes simple was performed in vitro using cultures of tissues of different origin: a primary culture of cells of the renal tissue of the human fetus (PAC) and diploid cell culture of fetal lung tissue of a person (LAC).Infection was performed using strains of the international collection of viruses: referee strain of herpes simplex virus serotype I (HSV-I) and referee strain of herpes simplex virus serotype 2 (HSV-2), and also introduced strains isolated in 1993 HSV-1/S-Petersburg/51/93 and HSV-2/C. Petersburg/60/93.The antiviral activity was performed according to the modified method M. Fujihara (1989). Prepared solutions of the drug Polyrem with a concentration of 500; 250; 125; 62,5; of 31.25 mg/ml in the medium Needle, introduced in 0.8 ml of solution in the sample cell culture and after contact with the cells for 2 hours was added to 0.2 ml vaccinated liquids of different dilutions and the resulting system was kept in the course is elaa the difference in titles, expressed in lg TCD50(tissue cytopathogenic doses). In this procedure, the drug is considered effective if the difference between the titles is 3.0 or more logarithms. The difference of the logarithms from 2.0 to 3.0 characterizes sufficient efficacy.Studied drug polyrem in these experimental conditions was reduced contagious herpes virus studied Shlemov on average 2.5 logarithm, which indicates an effective antiviral effects of the drug.Clinical approbation of polyrem against herpes virus was carried out on the basis of the Institute of obstetrics and gynecology. D. O. Ott in the treatment of 32 patients with recurrent herpetic infection.Among the observed 21 patients had recurrent genital herpes and 11 patients were with recurrent labialis herpes. More patients previously until the next recurrence of the symptoms of herpes infection underwent therapy with acyclovir or less effective means of bonafton, alpizarinom.The drug polyrem used for therapeutic and prophylactic regimens. When the medical scheme in the acute period (rash), the drug was applied for 3 days 2 tablets is etki 1 every 3 days.The effectiveness of the drug in the acute period was assessed by the reduction of lesions and reduce their intensity.The effectiveness of the drug in miracidial period was assessed by the prolongation of remission and reduce the intensity of the rash in case of their occurrence.The level of immune response in patients who polyrem established in their laboratory examination and determination of T-lymphocyte-helpers, T-suppressors, functional activity of NK-cells.On the basis of clinical observations and laboratory findings of patients who took the drug polyrem, installed
the drug polyrem in the treatment of herpes in the acute period was effective in 70% of the observed patients;
polyrem had a positive effect in the prevention of recurrences of herpetic infection in 50% of patients taking the drug.The results of the laboratory examination of patients indicate increased activity of NK-cells and T-lymphocytes-lymphocytes in patients treated polyrem. The obtained data indicate that stimulation of the immune response and increase the level of immune protection.A high level of preventive and curative depraverat.Example 10. Patient C. for 30 years. Turned 13.01.93.12-13 years recurrent h. labialis. Until September 1993, exacerbation was repeated 3-4 times a year and have been associated generally with acute respiratory diseases. Herpetic lesions appear on the mucosa of both the lips and the nose wings. From September 1993 to January 1994 relapses were 5 times. This has increased the bridgehead and the intensity of the lesion is more abundant rash began to appear in the sky and language. In November 1993, began to appear hermetic rash on the right shoulder. At the time of treatment was observed herpetic rash in the area of the lips, nose wings (second day), and the patient has used oksolinovoj ointment and disinfectant drugs (brilliant green).The patient underwent a course of therapy, including tablets polyrem (2 tablets a day for 3 consecutive days) and the application of ointments containing polyrem 10% methylcellulose 2,5% nipagin-nipazol 0.2% and water of 87.3%
The result of therapy was observed rapid reduction of lesions within 2 days instead of the usual 5 days. To the current time after six months of follow-up of exacerbations h. labialis was not observed.Example 11. Patient 21 So he Turned 24.03.92, Trenitalia. Similar manifestations of h. genitalis was repeated in January 1992, Since herpes in the field of external genitals bothered almost every month, mainly in the period of menstruation, and tended to increase the lesions. In miracidial period are often concerned about itching and mild vaginal discharge.By the time of treatment the patient has been bonafton, alpizarin, helpin used UBI. Once took a course wireless. A clear positive effect was not received.From epidemiological history established that the husband is somewhat less than the patient, but also symptoms of h. genitalis. At the time of treatment was observed abundant herpetic rash in the area of the labia majora and perineum in various stages of vesicles, erosion, crust.The patient was prescribed a course of treatment polyrem 2 tablets a day for 3 consecutive days. On the background of the drug was observed accelerated reduction of lesions within 2 days, while typically the aggravation of the patient lasted for at least 8-10 days.The following disease recurrence occurred in 3 months, and the treatment was carried out already on the first day of aggravation that p is profilakticheski of treatment polyrem. The drug was taken 3 times 2 tablets every 2 days.During the past period to the time of observation in may 1994, the recurrence of herpetic infection is not more than 1 time per year in reduced form.In addition polyrem applied only estateservices funds (furacin), a solution of potassium permanganate).Thus, the use of polyrem significantly reduce the frequency and intensity of lesions h. genotalis.Example 12. The patient Was 31 years old. Turned 11.02.94,From November 1993 worried about relapsing h. labialis. By the time of treatment 4 times appeared abundant herpetic eruptions on both the lips and nostrils.Epidemiological anamnesis calm. History 2 miscarriages, diffuse non-toxic goiter, ovarian failure. By the time the treatment is virtually no anti-herpes treatment is not received.At the time of initial treatment of any manifestations of h. labialis was not. Re 24.02.94 in the I-th day of the acute relapse h. labialis. Observed abundant typical rash h. labialis on both lips in vesicle stage. Individual vesicles revealed, and in their place have formed the,8% Processing affected surfaces was carried out from the first day of exacerbation. Against this background, stopped the formation of new vesicular elements. Already formed vesicles have dried up, and other epithelialize within 2 days. In General, the duration of exacerbation was reduced to 3 days compared to the usual course of relapse up to 5-7 days.Prevention of tick-borne encephalitis is carried out by vaccine killed vaccine, which should be held three times during the month, ahead of a possible infection. The required level of protection develops after revaccinate for 3-4 years, which is in practice difficult to implement (I. I. Kamalov. Live vaccine against tick-borne encephalitis problems and prospects. St. Petersburg, 1991).The specificity of the treatment of tick-borne encephalitis immune status and total resistance to treatment mainly use-globulin recovered from encephalitis. There are the results of laboratory tests showing antiviral activity of rimantadine during infection of tick-borne encephalitis.The effectiveness of polyrem against tick-borne encephalitis virus was identified on the model of infection of mice with the introduction of tick-borne encephalitis virus, strain Absettarov allocated to the administration of the virus, cultured in brain tissue of mice. Infection was carried out at the introduction of 0.2 ml/mouse of a suspension of brain tissue in saline solution (aqueous solution of NaCl c mass fraction of 0.85%) containing 1-10 LD50of the virus.In the experimental groups of animals were injected polyrem oral dose at each meal 2 mg/mouse (130 mg/mg) in terms of the content of rimantadine-base drug.The introduction of the drug was carried out under different schemes. Polyrem was administered once for 24 h before infection (scheme I) or for I h before infection (figure 2). Polyrem was injected three times for 1 h before infection and after 48 and 96 h after infection (figure 3). Polyrem was administered for 24 h, then for 1 h before infection and 24 h after (scheme 4). The introduction of the drug was carried out for 24 h before infection and after 4 h and then at 24 h after (scheme 5).Under the scheme with a six-fold by the introduction of a single dose was 1 mg/mouse, and the drug was administered 1 h before and 24, 48, 72, 96 and 120 h after infection (figure 6).In the same way (6) was administered rimantadine hydrochloride.Efficacy was assessed by the level of mortality compared with the control group of mice who were given placebo (fiziologicheskii marked reduction in death of the infected mice (table.3). The effect was achieved already after a single dose of the drug. Higher efficiency with the introduction for medical schemes (3 and 6) due to the feature of the pathogenesis of infection with tick-borne encephalitis, which is characterized by a two-over. The observed differences in rates of protection of the drug under different schemes of its introduction are subject to certain fluctuations in mortality in the control groups.Rimantadine hydrochloride has a protective antiviral long-term effects on medical scheme (6). When using polyrem the same effect is achieved already after a single dose of the drug and consequently decreasing its dose rate 2.5 times in terms of rimantadine (PL.4).Thus, polyrem can be used as an effective means of preventing tick-borne encephalitis and if necessary further treatment.Thus, the developed new domestic drug with a wide spectrum of action. The proposed drug Polyrem has prolonged antiviral activity against herpes viruses type I and II, tick-borne encephalitis, influenza virus type a, shows antitoxin the period of application of the proposed drug and clinical observations were noted adverse reactions, associated with his reception.The drug is recommended for the prevention and treatment of influenza infection of different etiology, acute respiratory infections, genital and labeling herpes encephalitis. Antiviral drug that contains the active substance on the basis of rimantadine and target additives, characterized in that the active substance it contains salt alpha-methyl-alpha - (1-substituted)methylamine, and copolymer of vinyl alcohol and N - vinylimidazole acid in the following ratio of components, wt.Salt of alpha-methyl-alpha - (1-substituted)methylamine 2,5 92,7
Additives target of 7.3 97,5
FIELD: medicine, pharmacy.
SUBSTANCE: invention proposes new tablets with size less 3 mm with sustained-releasing the opioid analgesic drug for 30 min in the amount above 75%. Invention provides opioid for oral intake with taking into account individual necessity of patient due to selection of required amount of mictotablets by dispenser.
EFFECT: valuable properties of tablet, expanded assortment of medicinal formulations of opioid analgesics.
19 cl, 4 tbl, 4 ex
SUBSTANCE: invention relates to pharmaceutical compositions in the form of cellular mechanically stable, lamellar, porous, spongy or foam-like structures and to a method for their preparing from solutions and dispersions. Method involves carrying out the following stages: a) preparing a solution or homogenous dispersion liquid and compound taken among the group including one or some pharmaceutically active compounds, one or some pharmaceutically acceptable additives and their mixtures, and the following stage b) foaming solution or homogenous dispersion at reducing pressure 30-150 torrs without boiling. Invention provides stabilizing the composition.
EFFECT: improved preparing method.
38 cl, 4 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to a tablet decomposing rapidly in the buccal pocket and comprising a medicinal agent, excipient and saccharide with relatively lower melting point than that of a medicinal agent and excipient. Tablet is made by uniform mixing saccharide with low melting point with tablet mass to form bridge between particles of named medicinal agent and/or excipient through melting product followed by hardening mentioned saccharide with low melting point. Except for, invention relates to a method for making tablet decomposing rapidly in buccal pocket and comprising a medicinal agent, excipient and saccharide with relatively lower melting point than that of medicinal agent and excipient. Method involves: (a) the parent components of tablet comprising a medicinal agent, excipient and saccharide with relatively lower melting point that that of a medicinal agent and excipient are pressed under low pressure to provide the required tablet form; (b) pressed product obtained after stage (a) is heated to temperature when saccharide with low melting point is melted; (c) melted product obtained after stage (b) is cooled to temperature when melted saccharide with low melting point is hardened. Invention represents a tablet decomposing rapidly in buccal pocket and having the tablet strength providing its using in tablet-making machines for dosed formulations and giving the possibility for making tablet using common tablet-making machines, and to a method for making tablets. Except for, invention represents a tablet decomposing rapidly in buccal pocket being this table as compared with common tablets has enhanced tablet strength and improved frangibility without prolonged decomposing time in buccal pocket, and a method for tablet making.
EFFECT: improved making method.
63 cl, 4 tbl, 1 dwg, 21 ex
SUBSTANCE: biologically active additive has propolis and pot marigold tincture, ascorbic acid, calcium gluconate, benadryl, rutin and auxiliary substances like starch, calcium stearate, talc taken in known proportion. The biologically active additive is produced as tablets of mass 0.55 g.
EFFECT: enhanced effectiveness of prophylaxis.
FIELD: medicine, pharmacy.
SUBSTANCE: invention discloses compositions with sustained-release of active component and masking taste that comprise one of more active components included in tricomponent matrix structure as a globule. This structure is formed successively by amphiphilic, lipophilic or inert matrices and included as globule or dispersed in hydrophilic matrix. Applying large amount of systems for regulation of dissolving active component provides modulating the dissolving rate of active component in aqueous and/or biological fluids by regulating thus kinetics in releasing active component in digestive tract.
EFFECT: valuable pharmaceutical properties of compositions.
14 cl, 14 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention describes composition of a pressed tablet comprising multiple of hardened melted granules of nonsteroid anti-inflammatory preparation (NSAID) with a melting point in the range 30-300oC and comprising a loosening agent dispersed uniformly in it. Granules comprise a continuum phase of indicated nonsteroid anti-inflammatory preparation and the table composition comprises additionally silicon dioxide in the amount 0.05-5.0% of composition mass. Preferably, the composition comprises also a nongranulated component containing silicon dioxide and excipient. The preferable NSAID represents ibuprofen that has a melting point in the range 75-77oC. Method provides preparing tablet showing useful industrial properties and ability for dissolving.
EFFECT: improved preparing method, valuable pharmaceutical properties of agent.
34 cl, 16 tbl, 64 ex
FIELD: medicine, pharmaceutical industry.
SUBSTANCE: invention proposes a preparation for regulation of respiratory organs function that is based on medicinal plants. The preparation comprises licorice roots dry extract, ginger milled roots, dry concentrates of creeping thyme herb and colt's foot leaves infusions, milled parmelia, hyssop herb dry concentrate, sage herb infusion dry concentrate, oat, ascorbic acid and accessory substances (starch, calcium stearate, sugar) taken in the definite ratio. The preparation is made as tablet with mass 0.55 g. The preparation promotes to effective regulation of respiratory organs function and elicits the expressed general tonic effect. The proposed preparation is used as an accessory agents promoting to regulation of function of respiratory organs.
EFFECT: valuable medicinal properties of supplement.
FIELD: pharmaceutical industry.
SUBSTANCE: ascorbic acid based vitamin composition contains magnesium stearate, ascorbic acid, and sodium ascorbate at ratio 2:3; mannitol and saccharose at ratio 1.445:1 in combination with other components (stearic acid and the like). Following proportions of ingredients are used: 58.2% ascorbic acid and sodium ascorbate, 1% magnesium stearate, and 40.8% other components.
EFFECT: improved characteristics without reduction in concentration of active substances, prolonged application time, improved appearance, and reduced use of constituents.
1 tbl, 11 ex
FIELD: medicine, gastroenterology, parapharmaceutical industry, phytotherapy.
SUBSTANCE: invention relates to industry manufacturing preparations for curative and prophylactic aims and can be used for prophylaxis and accessory treatment of digestion organs disease, in particular, diseases of pancreas. Invention proposes the preparation for prophylaxis and maintenance drug therapy in treatment of pancreas diseases in the tableted form based on medicinal plants. Invention proposes the preparation comprising dry concentrates of decoctions prepared from elecampane roots, burdock roots, barberry fruits, thyme seeds, flax seeds, buckwheat milled seeds, ascorbic acid, calcium gluconate, starch, calcium stearate and sugar taken in the definite ratio of components. Invention is directed for expanding assortment of medicinal agents used for therapy and prophylaxis of functional disorders in digestion tract function. The preparation exerts an astringent, antiseptic, moderate spasmolytic and analgetic effect, it normalizes acidity of gastric juice and improves digestive processes.
EFFECT: valuable medicinal properties of preparation.
FIELD: medicine, parapharmaceutical industry.
SUBSTANCE: invention relates to industry manufacturing preparations for curative and prophylactic aims and can be used as a curative and prophylactic, bactericidal, antiviral, anti-inflammatory, analgetic agent promoting to regulation of respiratory organs. The preparation eliciting anti-inflammatory and antibacterial properties comprises dry concentrate of propolis alcoholic tincture, ascorbic acid, fruit essence dry concentrate, citric acid, calcium stearate and sugar taken in the definite ratio of components. The preparation expands assortment of medicinal agents used for treatment of acute and chronic diseases of respiratory organs and represents alternative variant for cases with individual intolerance of some components.
EFFECT: valuable medicinal properties of preparation.